Human Uterus Transplantation: Have We Opened a Pandora's Box?

Abstract

The only untreatable subgroup of female infertility is absolute uterine factor infertility (AUFI), which is due to congenital or surgical absence of a uterus or presence of a non-functional uterus. The solitary option for a woman with AUFI to become a biological mother today is through a gestational surrogacy, a procedure that is outlawed in many countries globally. Human uterus transplantation is a potential future treatment of AUFI. Akar et al. from Turkey reported the first clinical pregnancy in 2013 after uterus transplantation in a 23-year-old Mayer-Rokitansky-Kuster-Hauser syndrome patient with previous vaginal reconstruction and uterus transplantation [2]. 18 months after the transplant, the endometrium was prepared for transfer of the thawed embryos. The first ET cycle with a single, day-3 thawed embryo resulted in a biochemical pregnancy. The second ET cycle resulted in a clinical pregnancy confirmed with transvaginal ultrasound visualization of an intrauterine gestational sac with decidualization. This pregnancy unfortunately did not grow further. Uterine transplantation requires extensive evaluation of the recipient and donor by an experienced multidisciplinary transplantation team both pre- and post-operatively [3]. Eleven human uterine transplantation attempts had been done worldwide but no live birth had yet been reported till 2014. In 2013, a 35-year-old woman with congenital absence of the uterus (MRKH syndrome) underwent transplantation of the uterus in Sahlgrenska University Hospital, Gothenburg, Sweden [4]. The uterus was donated from a living, 61-year-old, parous donor. In vitro fertilization treatment of the recipient had been done before transplantation, from which 11 embryos were vitrified. The recipient and the donor had essentially uneventful post-operative recoveries. The recipient’s first menstruation occurred 43 days after transplantation, and she continued to menstruate at median intervals of 32 days. 1 year after transplantation, the recipient underwent her first single embryo transfer, which resulted in pregnancy. She was then given triple immunosuppression (Tacrolimus, Azathioprine, and Corticosteroids), which was continued throughout pregnancy. She had three episodes of mild rejection, one of which occurred during pregnancy. These episodes were all reversed by corticosteroid treatment. Fetal growth parameters and blood flows of the uterine arteries and umbilical cord were normal throughout pregnancy. The patient was admitted with pre-eclampsia at 31 full weeks and 5 days, and 16 h later a cesarean section was done because of an abnormal cardiotocogram. A male child with a normal birth weight for gestational age (1775 grams) and with APGAR scores 9, 9, and 10 was born. Brannstrom et al. thus described the first live birth after human uterus transplantation [4].